The effect of over expression of Pdx1 and Foxa2 on the differentiation of human embryonic stem cells into pancreatic cells

¹ Department of Genetics, The Institute of Life Sciences, The Hebrew University, Jerusalem, Israel

^* To whom correspondence should be addressed. E-mail: nissimb{at}mail.ls.huji.ac.il.

	Abstract

Human embryonic stem cells (HESCs) are pluripotent cells that may serve as a source of cells for transplantation medicine, and as a tool to study human embryogenesis. Using genetic manipulation methodologies, we have investigated the potential of HESCs to differentiate into the various pancreatic cell types. We initially created various HESCs carrying the enhanced green fluorescent protein (eGFP) reporter gene under the control of either the insulin promoter or the pancreatic and duodenal homeobox factor-1, Pdx1, promoter. Our analysis revealed that during the differentiation of HESCs into embryoid bodies (EBs), we could detect green fluorescent cells when eGFP is regulated by Pdx1 promoter but not by insulin promoter. In order to examine whether we can induce differentiation into pancreatic cells, we have established human embryonic stem cell lines that constitutively express either Pdx1 or the endodermal transcription factor, Foxa2. Following differentiation into EBs the constitutive expression of Pdx1 enhanced the differentiation of HESCs towards pancreatic endocrine and exocrine cell types. Thus, we have demonstrated expression of several transcription factors that are downstream to Pdx1 and various molecular markers for the different pancreatic cell types. However, the expression of the insulin gene could be demonstrated only when the cells differentiated in vivo into teratomas. We conclude that although over-expression of Pdx1 enhanced expression of pancreatic enriched genes, induction of insulin expression may require additional signals that are only present in vivo.

This article has been cited by other articles:

				S. Ilancheran, A. Michalska, G. Peh, E. M Wallace, M. Pera, and U. Manuelpillai Stem Cells Derived from Human Fetal Membranes Display Multilineage Differentiation Potential Biol Reprod, September 1, 2007; 77(3): 577 - 588. [Abstract] [Full Text] [PDF]

				J. Jiang, M. Au, K. Lu, A. Eshpeter, G. Korbutt, G. Fisk, and A. S. Majumdar Generation of Insulin-Producing Islet-Like Clusters from Human Embryonic Stem Cells Stem Cells, August 1, 2007; 25(8): 1940 - 1953. [Abstract] [Full Text] [PDF]